中国动脉硬化杂志2025，Vol.33Issue(8)：665-672,8.DOI:10.20039/j.cnki.1007-3949.2025.08.003
PIAS3缺失促进雌性ApoE基因敲除小鼠动脉粥样硬化发展
PIAS3 deficiency exacerbates the development of atherosclerosis in female ApoE knock-out mice
摘要
Abstract
Aim To investigate whether protein inhibitor of activated STAT3(PIAS3)deficiency exacerbates the occurrence and development of atherosclerosis(As)in female ApoE knockout mice.Methods PIAS3 gene knockout mice with ApoE-/-background(PIAS3-/-/ApoE-/-)and their littermate PIAS3+/+/ApoE-/-mice were bred and fed with a high-fat/high-cholesterol diet for 12 weeks to induce As.Body weight(every week)and plasma lipid levels including to-tal cholesterol,triglyceride,high density lipoprotein cholesterol and non-high density lipoprotein cholesterol(every 4 weeks)of the mice were measured.Oil red O staining,HE staining,immunohistochemistry staining and immunofluores-cence staining were performed on mouse aortic tree and frozen sections of aortic root to evaluate the area,cellular composi-tion and stability of As plaques.Moreover,the expression of estrogen receptor α(ERα)and its co-localization with vas-cular smooth muscle cells(VSMC)in plaques were determined by immunofluorescence staining.Results Compared with PIAS3+/+/ApoE-/-mice,PIAS3-/-/ApoE-/-mice showed no significant differences in body weight,major organ weight(heart,liver,spleen,kidney and epididymal fat)and plasma lipid levels;however,PIAS3 deficiency promoted the forma-tion of As in female PIAS3-/-/ApoE-/-mice.Compared with PIAS3+/+/ApoE-/-mice,PIAS3-/-/ApoE-/-mice showed an increased lipid accumulation and a decreased VSMC content in As plaques(P＜0.05),leading to a decrease in plaque stability.In addition,the expression of ERα in the As plaques of PIAS3-/-/ApoE-/-mice was significantly downregulated(P＜0.05),and there was a obvious co-localization between ERα and VSMC.The reduction of VSMC content in PIAS3-/-/ApoE-/-mouse plaques might lead to a decrease of ERα expression,thereby weakening the anti-As effect of es-trogen.Conclusion PIAS3 deficiency exacerbates the formation of As plaques in female PIAS3-/-/ApoE-/-mice,which might be due to the regulatory effect of PIAS3 on ERα expression in plaques.关键词
动脉粥样硬化/活化STAT3蛋白抑制因子/雌激素受体/血管平滑肌细胞Key words
atherosclerosis/protein inhibitor of activated STAT3/estrogen receptor α/vascular smooth muscle cell分类
医药卫生引用本文复制引用
李超超,黄会紫,张璟怡,费浩,杨立伟,王蓉..PIAS3缺失促进雌性ApoE基因敲除小鼠动脉粥样硬化发展[J].中国动脉硬化杂志,2025,33(8):665-672,8.基金项目
国家自然科学基金项目(82170471) （82170471）
陕西省自然科学基础研究项目(2023-CX-PT-01) （2023-CX-PT-01）
